The stages in the pathogenesis of gallstones are: 1) formation of abnormal or lithogenic bile saturated or supersaturated with cholesterol; 2) nucleation and precipitation of cholesterol crystals; and 3) growth or conglomeration of these crystals. Bile acids and lecithin are the primary solubilizing agents for cholesterol in bile. Recent evidence has implicated a defect in hepatic enzymatic metabolism that may relate to secretion of saturated bile. Chenodeoxycholic acid causes an increase in cholesterol secretion and bile acid pool size which leads to a decrease in the cholesterol saturation of bile and gallstone dissolution. The objectives and methods of this research program are to: 1. Investigate the characteristics of lithogenicity and the pathogenesis of cholelithiasis by study of: a. The relative bile acid, lecithin and cholesterol concentrations in bile using duodenal drainage; b. The kinetics of bile acid metabolism using C14, tritiated and deuterated bile acids to determine synthesis rate and pool size; c. Hepatic enzymatic formation of bile acids and cholesterol by in vitro assays on liver tissue and, d. Study of biliary lipid secretion in isolated hamster liver. 2. Investigate the effects including toxicity and mechanisms of bile acids and phenobarbital on: a. The cholesterol saturation of bile and on gallstone dissolution in man; b. The rate limiting enzymes of cholesterol synthesis (HMG CoA reductase) and bile acid synthesis (7-alpha-hydroxylase) in hamster and human liver.